Gitelman syndrome E26.8

Aostosoma recessive disease associated with hypokalemic alkalosis, salt wasting, renewed blood pressure, hypomagnesemia, and hypocalciuria.

The prevalence is estimated to be about 1:40,000 in populations of European origin, i.e. about 1% are heterozygous (recessive inheritance). It is thus one of the most common hereditary renal tubulopathies. Symptoms usually do not appear before the age of 6 years.

Gitelman syndrome is inherited in an autosomal recessive manner.

In most patients, mutations are found in the SLC12A3 gene (solute carrier family 12 member 3, 16q13). It encodes the thiazide-sensitive Na-Cl cotransporter (NCC).

To date, >150 different NCC mutations of the gene have been described. They affect the sodium-chloride cotransporter in the distal tubule of the nephron.

In a few patients with Gitelman syndrome (as in type III of Bartter syndrome = classical type) mutations were found in the CLCNKB gene (localization: 1p36). This gene codes for the renal chloride channel B (ClC-Kb).

The diagnosis follows from the clinical symptoms and the biochemical changes (hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria).

Substitutive potassium and magnesium regulation; prostaglandin synthesis inhibitors; spironolactone or triamterene.

1. Fulchiero R et al (2019) Bartter syndrome and Gitelman syndrome. Pediatr Clin North Am 66:121-134.
2. Knoers NV et al (2008) Gitelman syndrome. Orphanet J Rare Dis 3:22.